A-Acetoxy ketones

Methylthiomethyl p-tolyl sulfone, 192 Potassium ruthenate, 259 Trimethylsilyl chlorochromate, 327 a-Substituted ketones (see also Halo carbonyl compounds, Hydroxy aldehydes and ketones) a-Acetoxy ketones Benzeneselenenyl chloride-Silver acetate, 27... 

Metal-ammonia solutions reduce conjugated enones to saturated ketones and reductively cleave a-acetoxy ketones i.e. ketol acetates) to the unsubstituted ketones. In both cases the actual reduction product is the enolate salt of a saturated ketone this salt resists further reduction. If an alcohol is present in the reaction mixture, the enolate salt protonates and the resulting ketone is reduced further to a saturated alcohol. Linearly or cross-conjugated dienones are reduced to enones in the absence of a proton donor other than ammonia. The Birch reduction of unsaturated ketones to saturated alcohols was first reported by Wilds and Nelson using lithium as the reducing agent. This metal has been used almost exclusively by subsequent workers for the reduction of both unsaturated and saturated ketones. Calcium has been preferred for the reductive cleavage of ketol acetates. 

Reductions of unsaturated ketones and a-acetoxy ketones usually are effected with an excess of reducing agent. For optimum yields of saturated ketones, the intermediate enolate salt obviously must not become protonated while... 

A third type of reduction of a-substituted ketones is typified by the expulsion of the substituent and the reduction of the keto function to form an olefin. Wolff-Kishner reductions of a-hydroxy, a-acetoxy, " a-halo, °° and a-epoxy (see below) ketones are the most frequently encountered steroid examples of this general class. ... 

Lead tetraacetate can effect oxidation of carbonyl groups, leading to formation of a-acetoxy ketones,215 but the yields are seldom high. Boron trifluoride can be used to catalyze these oxidations. It is presumed to function by catalyzing the formation of the enol, which is thought to be the reactive species.216 With unsymmetrical ketones, products from oxidation at both a-methylene groups are found.217... 

Introduction of oxygen a to a ketone function can also be carried out via the silyl enol ether. Lead tetraacetate gives the a-acetoxy ketone.219... 

Reduction of 2-bromo-3-pentanone at mercury affords a mixture of 3-pentanone and l-hydroxy-3-pentanone, whereas electrolysis of Q ,Q -dibromoacetone in the presence of benzoate gives a mixture of products arising from both a carbon-bromine bond cleavage and an Sn2 displacement of bromide by benzoate [94]. In an acetic acid-acetate buffer, branched dibromo ketones, such as 2,4-dibromo-2,4-dimethyl-3-pentanone, are reduced to a-acetoxy ketones however, less highly substituted compounds, such as 4,6-dibromo-5-nonanone, undergo simple cleavage of both carbon-bromine bonds [95]. Other work dealing with the reduction of Q, Q -dibromoketones has been described [96]. 

Oxidative electrophilic activation of a, f-unsaturated phenylsulfides, carried out in an AcOH/AcONa solution results in products of the addition of a nucleophile to the multiple bonds, a,y3-diacetoxysulfides or, as a result of a further oxidation, that eliminates the PhS group, in a-acetoxy ketones (Scheme 23) [89]. 

Electrochemical reduction of a,a -dibromoketones affords the unstable cyclo-propanone, which is in equlibrium with the dipolar intermediate 22. The cyclopro-panone hemiacetal is isolated in yields of 40 - 85 % from reaction in acetonitrile and methanol at -20 °C [99], The dipolar form can be trapped in a cycloaddition process with furan [100], Reaction with acetic acid leads to the a-acetoxy-ketone.[101]. Unstable three membered heterocyclic rings are intermediate in the reduction of sulphur and phosphorus linked dibromo compounds 23. In these reactions, the heteroatom is extruded leaving ci - and trans-stilbenes as the isolated products [102,103],... 

Furthermore, yeast treatment of the a-acetoxy ketone 53, bearing two oxygen substituents ( ) at a and affords the carbinol 54 in 20 % yield, somewhat less than 10 % of the (2R) diastereoisomer, and 70 % of recovered starting material. From the carbinol 54, crystalline 55 is obtained, which may be converted through suitable manipulation of the protecting groups and ozonolysis, into A-deoxy-D-talo-hexose 56. The minor diastereoisomer similarly affords A-deoxy-D-xylo-hexose 57. Thus, in the yeast treatment of 53, as the results of the enzymic kinetic resolution, the (2S, 4S, 5R) diol 55, a carbohydrate-like chiral synthon, is accessible out of eight possible isomers. 

Enol acetates form epoxides which can rearrange to a-acetoxy ketones ... 

The oxidation of enol acetates of ketones to a-hydroxy (or a-acetoxy) ketones with the BTSP-FeCls system can also be performed . 

A particular class of quinoxaline A-oxides can be synthesized by a reaction sequence starting from condensation of anilines with a-oximino ketones (Scheme 50) <1998S1769>. The key step is oxidation of the oxime to an a-acetoxy nitroso group, which behaves as an electrophile leading to the formation of the quinoxaline ring. 

Die Methode ist sehr breit anwendbar (s. S. 10) und bietet gegeniiber der Radziszewski-Reaktion den Vorteil, daB man die oft schwierig herzustellenden und empfindlichen a-Dicarbonyl-Ver-bindungen nicht isolieren muB. Die a-Hydroxy-ketone bzw. die entsprechenden a-Acetoxy-ketone werden im allgemeinen mit Kupfer(ll)-acetat, Ammoniak und dem Aldehyd in Wasser oder Wasser/Alkohol-Gemischen umgesetzt. 

Als Nebenprodukte entstehen oft 1,3-Oxazole (vgl. Bd. E8a, S. 903, 911). a-Hydroxy- und a-Acetoxy-ketone liefern die entsprechenden 1,3-Oxazole sogar als Hauptprodukte42,43. Aus 3-Brom-l-oxo-l-phenyl-butan erhalt man mit Ammoniumformiat in Ameisensaure 4-Ethyl-5-phenyl-imidazolin 75% Ausbeute. Dagegen entsteht aus dem isomeren l-Brom-2-oxo-l-phenyl-butan unter analogen Reaktionsbedingungen das entsprechende 1,3-Oxazol in iiber 70% Aus-... 

The trisubstituted alkene of 10 was more readily oxidized than was the congested tetrasubstituted alkene, so the more reactive alkene was temporarily epoxidized. After ozonolysis, the epoxide was reduced off using the Sharpless protocol. It is a tribute to the specificity of this reagent that the easily-reduced a-acetoxy ketone is not affected. Selective silylation of the more accessible ketone followed by melhylenation, hydrolysis and addition of methyl lithium to the outside face of the previously protected carbonyl then delivered 1. 

Norbomenes specifically undergo Pd(0)-catalyzed cyclopropanation by 1 -acetoxy-3-silyl-2-propanones to afford acetylcyclopropane-annelated products349. Methyleneoxazolidinones, ketone a-carbonates and 5-methylene-l,3-dioxolane-2-ones can also be used as the cyclopropanation reagent (equation 157)350 352. 

Reduction of a-alkoxy ketones.2 a-Hydroxy ketones are reduced by Sml2 in THF/CH3OH in rather low yield ( 30%). In contrast a-acetoxy ketones are reduced in >75% yield. A simple expedient is to reduce the a-hydroxy ketone in the presence of AczO with Sml2 (equation I). a-Silyloxy, benzoyloxy, and tosyloxy... 

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